Overview of the updated antiemetic guidelines for chemotherapy-induced nausea and vomiting

nausea and vomitingRudolph M. Navari, MD, PhDIndiana University School of Medicine–South Bend, South Bend, IN Nausea and vomiting associated with cancer chemotherapy are experienced by 70%–80% of patients receiving chemotherapy and can result in significant morbidity. Chemotherapy-induced nausea and vomiting (CINV) adversely affects patient quality of life, often leading to poor compliance with the treatment regimen and serious metabolic complications. Several classes of antiemetic drugs are available to prevent or treat CINV. Older agents include phenothiazines, antihistamines, and corticosteroids. Serotonin (5-HT3) receptor antagonists became available in the 1990s for use in preventing CINV. Recently, the NK1 receptor antagonist aprepitant was introduced for use in combination therapy regimens. Despite this introduction of new and more effective antiemetic agents, emesis remains a significant complication of chemotherapy. Updated antiemetic guidelines were published in 2007 by the National Comprehensive Cancer Network and in 2006 by the American Society of Clinical Oncology. Updates for clinicians who treat patients with CINV are now available and are reviewed here.
C hemotherapy-induced nausea wound dehiscence.1,11 Patients who are dehydrated, debilitated, or malnourished, as well as those who have an electrolyte imbalance or those who have re- cently undergone surgery or radiation therapy, are at greater risk of experiencing serious complications dergoing chemotherapy experience emesis, with Despite the recent introduction of new and 10%–44% experiencing anticipatory emesis.1,2 more effective antiemetic agents, emesis remains CINV results in significant morbidity and neg- a significant complication of chemotherapy. Up- atively impacts patient quality of life.3–5 CINV dated antiemetic guidelines were published in 2007 may cause nonadherence to chemotherapy or by the National Comprehensive Cancer Network dose reductions due to anticipatory nausea and (NCCN) and in 2006 by the American Society of Increased risk of CINV is associated with the Manuscript received February 15, 2007; accepted March 1, following factors: age < 50 years, female gender, vomiting during previous chemotherapy, preg- Funding for this publication was provided by Roche Labora- nancy-induced nausea/vomiting, history of mo- Correspondence to: Rudolph M. Navari, MD, PhD, Professor tion sickness, and anxiety.9,10 CINV can result in of Medicine, Assistant Dean, and Director, Indiana University weakness, weight loss, electrolyte imbalance, dehy- School of Medicine–South Bend, 100 Raclin-Carmichael Hall, dration, or anorexia and is associated with a variety 1234 Notre Dame Avenue, South Bend, IN 46617; telephone: of complications, including fractures, esophageal 574-631-3793; fax: 574-631-4939; e-mail: [email protected]. tears, decline in behavioral and mental status, and Commun Oncol 2007;4(suppl 1):3–11 2007 Elsevier Inc. Al rights reserved.
April 2007 ■ COMMUNITY ONCOLOGY 3
Pathophysiology of
nausea and vomiting
Types, causes, and risk
categories of CINV
derly patients (> 65 years of age) are or requires “rescue” is called break- 4 COMMUNITY ONCOLOGY ■ April 2007
Updated antiemetic guidelines for chemotherapy-induced nausea and vomiting TABLE 1
Emetic risk of antineoplastic agents
High emetic risk
Moderate emetic risk
Low emetic risk
Minimal emetic risk
(> 90% frequency
(30%–90% frequency
(10%–30% frequency
(< 10% frequency of
of emesis)*
of emesis)*
of emesis)*
emesis)*
* Proportion of patients who experience emesis in the absence of effective antiemetic prophylaxis† Daily use of antiemetics is not recommended based on clinical experienceAdapted, with permission from the American Society of Clinical Oncology,19 with additional information.1 Principles in the
management of CINV
unless specifically stated.1,17 The 2006 forth several principles of effective an- dition to patient-specific risk factors.
emetic risk (the risk of emesis persists Antiemetic agents
April 2007 ■ COMMUNITY ONCOLOGY 5
Antiemetic recommendations by emetic-risk categories Emetic-risk category
ASCO guidelines
NCCN guidelines
Three-drug combination of a 5-HT3 receptor Before chemotherapy, a 5-HT3 receptor antagonist antagonist, dexamethasone, and aprepitant (ondansetron, granisetron, dolasetron, or palono- setron*), dexamethasone (12 mg), and aprepitant (125 mg) recommended, with or without lorazepam For patients receiving cisplatin and all other For prevention of delayed emesis, dexamethasone agents of high emetic risk, the two-drug (8 mg) on days 2–4 plus aprepitant (80 mg) on combination of dexamethasone and aprepitant days 2 and 3 recommended, with or without recommended for prevention of delayed emesis For patients receiving an anthracycline and For patients receiving an anthracycline and cyclophosphamide, the three-drug combination cyclophosphamide and selected patients receiving a 5-HT3 receptor antagonist, dexamethasone, and other chemotherapies of moderate emetic risk (eg, aprepitant recommended before chemotherapy; carboplatin, cisplatin, doxorubicin, epirubicin, single-agent aprepitant recommended on days 2 ifosfamide, irinotecan, or methotrexate), a 5-HT3 receptor antagonist (ondansetron, granisetron, For patients receiving other chemotherapies of dolasetron, or palonosetron*), dexamethasone moderate emetic risk, the two-drug combination of (12 mg), and aprepitant (125 mg) recommended, a 5-HT3 receptor antagonist and dexamethasone with or without lorazepam, before chemotherapy; recommended before chemotherapy; single-agent for other patients, aprepitant is not recommended dexamethasone or a 5-HT3 receptor antagonist For prevention of delayed emesis, dexamethasone suggested on days 2 and 3 for prevention of (8 mg) or a 5-HT3 receptor antagonist on days 2–4 or, if used on day 1, aprepitant (80 mg) on days 2 and 3, with or without dexamethasone (8 mg) on days 2–4, recommended, with or without Dexamethasone (8 mg) suggested; no routine Metoclopramide, with or without diphenhydramine; preventive use of antiemetics for delayed emesis dexamethasone (12 mg); or prochlorperazine No antiemetic administered routinely before or No routine prophylaxis; consider using antiemetics listed under primary prophylaxis as treatment * Order of listed antiemetics does not reflect preferenceASCO = American Society of Clinical Oncology; NCCN = National Comprehensive Cancer Network; 5-HT3 = 5-hydroxytryptamineAdapted, with permission, from the American Society of Clinical Oncology18 Reproduced and adapted with permission from the NCCN 1.2007 Antiemesis Guidelines.1 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. To view the most recent and complete version of the guideline, go online to www.nccn.org.
Intravenous (IV)
* The FDA-approved IV dose of granisetron is 0.01 mg/kg.
Adapted, with permission, from the American Society of Clinical 6 COMMUNITY ONCOLOGY ■ April 2007
Updated antiemetic guidelines for chemotherapy-induced nausea and vomiting Efficacy and safety
of antiemetic agents
in clinical trials
April 2007 ■ COMMUNITY ONCOLOGY 7
Pharmacologic management
by emetogenic potential
the historic control group (0%; P < 8 COMMUNITY ONCOLOGY ■ April 2007
Updated antiemetic guidelines for chemotherapy-induced nausea and vomiting References
in Oncology; v.1.2007: Antiemesis. Avail-able at: http://www.nccn.org/profession- als/physician_gls/PDF/antiemesis.pdf. Ac- McArdle CS. Incidence of nausea and vomit- ing with cytotoxic chemotherapy: a prospec- tive randomised trial of antiemetics. Br Med J nausea and vomiting—incidence and impact Drug regimens for
on patient quality of life at community oncol- ogy settings. Support Care Cancer 2006 Nov special categories of
nausea and vomiting
Conclusion
P, Hansen M, Herrstedt J. Delayed nausea and vomiting continue to reduce patients’ quality of life after highly and moderately emetogenic chemotherapy despite antiemet- affect a patient’s quality of life, and ic treatment. J Clin Oncol 2006;24:4472– Kaizer L, Pater J. Effect of postchemotherapy nausea and vomiting on health-related qual- ity of life. The Quality of Life and Symptom Control Committees of the National Cancer Institute of Canada Clinical Trials Group. Support Care Cancer 1997;5:307–313.
6. Gralla RJ, de Wit R, Herrstedt J, et al. Antiemetic efficacy of the neurokinin-1 an- tagonist, aprepitant, plus a 5HT3 antagonist and a corticosteroid in patients receiving an- thracyclines or cyclophosphamide in addi- tion to high-dose cisplatin: analysis of com- bined data from two phase III randomized clinical trials. Cancer 2005;104:864–868.
Incidence and duration of chemotherapy-induced nausea and vomiting in the out- patient oncology population. J Clin Oncol The influence of symptoms of disease and side effects of treatment on compliance with cancer therapy. J Clin Oncol 1988;6:1746– April 2007 ■ COMMUNITY ONCOLOGY 9
diotherapy-induced nausea and vomiting: a tagonist for chemotherapy-induced nausea nausea and vomiting: state of the art in 2006. J comparison with other antiemetic therapies. Support Oncol 2006;4(2 suppl 1):3–8.
Support Care Cancer 2005;13:671–678.
PJ, et al. Single-dose oral granisetron has agents and definition of antineoplastic agent ics: evidence-based, clinical practice guide- equivalent antiemetic efficacy to intrave- lines. American Society of Clinical Oncol- ogy. J Clin Oncol 1999;17:2971–2994.
cisplatin-based chemotherapy. J Clin Oncol ity of chemotherapeutic agents. Semin Oncol is a major enzyme responsible for the metab- L, Tfayli A. Relative efficacy of ondansetron, olism of granisetron in human liver micro- granisetron, dolasetron and palonosetron in testinal disorders. In: Guyton AC, Hall JE. somes. Curr Drug Metab 2005;6:469–480.
controlling acute nausea and vomiting asso- Textbook of Medical Physiology. Philadel- ciated with platinum-based chemotherapy. J phia, Pa: Elsevier Saunders; 2006:823–824.
Flockhart DA. Interethnic differences in 13. Pasricha JP. Drugs affecting gastroin- testinal function. In: Hardman JG, Limbird U.S. population: clinical implications. On- et al. 5-Hydroxytryptamine-receptor antag- LE, eds. Goodman & Gilman’s The Phar- onists versus prochlorperazine for control 26. Kaiser R, Sezer O, Papies A, et al. Pa- of delayed nausea caused by doxorubicin: a York, NY: McGraw-Hill; 2001:1000–1005.
tient-tailored antiemetic treatment with 5-hy- droxytryptamine type 3 receptor antagonists 39. Jordan K, Grothey A, Kegel T, Fibich duced nausea and vomiting. Gastroenterol types. J Clin Oncol 2002;20:2805–2811.
C, Schobert C. Antiemetic efficacy of an oral suspension of granisetron plus dexamethasone Available at: http://www.tropisetron.com/ and influence of quality of life on risk for nau- fda_info/. Accessed January 12, 2007.
sea and vomiting. Onkologie 2005;28:88–92.
cancer chemotherapy. Support Care Cancer 5-HT3 receptor antagonists in the treatment al. Comparison of single-dose oral granise- of acute chemotherapy-induced nausea and tron versus intravenous ondansetron in the vomiting. Cancer Invest 2000;18:163–173.
prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a 17. Roila F, Hesketh PJ, Herrstedt J; An- M, et al. Comparison of the antiemetic effect multicenter, double-blind, randomized par- tiemetic Subcommittee of the Multinational allel study. J Clin Oncol 1998;16:754–760.
Association of Supportive Care in Cancer. and high-dose intravenous haloperidol in a 41. Silva RR, Bascioni R, Giorgi F, et al. randomized double-blind crossover study. J therapy-induced emesis: results of the 2004 ately emetogenic chemotherapy: evaluation Perugia International Antiemetic Consensus of activity during three consecutive cours- LB, Groshen S. Antiemetic control and pre- vention of side effects of anti-cancer therapy MR, et al. American Society of Clinical On- cology guideline for antiemetics in oncology: et al. Comparative clinical trial of granise- update 2006. J Clin Oncol 2006;24:2932– tron and ondansetron in the prophylaxis of domized trial. Cancer 1987;60:2816–2822.
cisplatin-induced emesis. The Granisetron Study Group. J Clin Oncol 1995;13:1242– SM, et al. Proposal for classifying the acute sert]. Indianapolis, Ind: Eli Lilly and Com- 43. Hesketh P, Navari R, Grote T, et al. Double-blind, randomized comparison of the et al. A phase II trial of olanzapine for the antiemetic efficacy of intravenous dolasetron prevention of chemotherapy-induced nausea mesylate and intravenous ondansetron in the with or without short-course dexamethasone prevention of acute cisplatin-induced emesis in the prophylaxis of radiation induced em- study. Support Care Cancer 2005;13:529– esis: a placebo-controlled randomized trial parative Chemotherapy-induced Emesis Pre- of the National Cancer Institute of Canada vention Group. J Clin Oncol 1996;14:2242– Clinical Trials Group (SC19). J Clin Oncol al. A phase I trial of olanzapine (Zyprexa) for the prevention of delayed emesis in can- al. Oral dolasetron mesylate in patients re- study. Cancer Invest 2004;22:383–388.
34. del Giglio A, Soares HP, Caparroz C, containing chemotherapy. Oral Dolasetron efficacy and safety of oral granisetron and Castro PC. Granisetron is equivalent to on- oral ondansetron in the prophylaxis of nau- dansetron for prophylaxis of chemotherapy- sea and vomiting in patients receiving hy- induced nausea and vomiting: results of a perfractionated total body irradiation. Bone meta-analysis of randomized controlled trials. Marrow Transplant 2000;26:203–210.
antagonist. Future Oncol 2006;2:591–602.
graeber M. Granisetron in the control of ra- 10 COMMUNITY ONCOLOGY ■ April 2007
Updated antiemetic guidelines for chemotherapy-induced nausea and vomiting RR, et al. Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, treatment for the anticipatory nausea and receptor antagonist: results of a phase III, vomiting induced by cancer chemotherapy. single-dose trial versus dolasetron. Cancer alone. J Clin Oncol 2001;19:1759–1767.
drugs for chemotherapy-induced emesis. Ex- et al. Acupuncture-point stimulation for Vegt S, et al. Palonosetron improves preven- pert Opin Emerg Drugs 2006;11:137–151.
ing. J Clin Oncol 2005;23:7188–7198.
et al. Establishing the dose of the oral NK1 ic chemotherapy: results of a double-blind antagonist aprepitant for the prevention of havioral intervention in cancer treatment: randomized phase III trial comparing sin- controlling aversion reactions to chemother- gle doses of palonosetron with ondansetron. apy. J Consult Clin Psychol 1982;50:1018– al. Efficacy and tolerability of aprepitant for GM, et al. A phase III, double-blind, ran- ABOUT THE AUTHOR
nausea and vomiting in patients with breast with ondansetron in preventing chemother- cancer after moderately emetogenic chemo- Affiliation: Dr. Navari is Professor of Medicine, Assistant Dean, and Director, Indiana Univer- apy-induced nausea and vomiting following therapy. J Clin Oncol 2005;23:2822–2830.
sity School of Medicine–South Bend, South role of psychological variables in post-che- Conflicts of interest: None disclosed.
motherapy nausea: anxiety and expectation. April 2007 ■ COMMUNITY ONCOLOGY 11

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